Overall: Project Summary/Abstract Native Americans in Maine, and people living in the Mystic River Watershed in Massachusetts have expressed serious concerns about contaminants in their environments. In both locations, people are negatively impacted by legacy contaminants, and in both cases, there are Environmental Justice communities of concern. The Loring Air Force Base Superfund site impacts the Native Americans, and the Industri-Plex, Wells G&H, and Olin Superfund sites impact people living in the Mystic River Watershed (a land area north and east of Boston, covering 76 square miles that drains into rivers feeding into the Boston Harbor). The MIT-SRP brings engineering and scientific innovation to bear on critical problems relevant to our stakeholders in Maine and Massachusetts. Our problem-oriented program centers around two pervasive contaminants, N-nitrosamines (potently carcinogenic to animals) and PAHs (carcinogenic to people). Both of these contaminants are broadly important as they are present in multiple Superfund sites and they continue to be produced by ongoing industrial activities today. The MIT-SRP with its diverse expertise (from engineers, to chemists, to biologists and to biological engineers) has the tools, the commitment, and the willingness to collaborate, making it possible to take on these serious environmental health challenges. Specifically, the MIT-SRP will: a) identify novel PAH breakdown products; b) develop novel sensor technologies including a low cost smartphone- enabled carbon nanotube sensor; c) use high fidelity duplex consensus sequencing to reveal patterns of mutations that can be traced to specific contaminants; d) reveal how age and stage of development impact susceptibility to N-nitrosodimethylamine and PAH-induced mutations and cancer; e) reveal how gene- environment interactions impact susceptibility to genomic instability and cancer; and f) use phosphoproteomics and transcriptomics to uncover systems-level molecular responses that shed light on underlying mechanisms of disease and give rise to novel biomarkers of disease risk. These tools will inform policy, enable risk estimates, and guide remediation. Our bi-directional program is based on established relationships with local agencies that represent our stakeholders. To maximize the impact of our Program, we will continue to grow our relationships with the Massachusetts Department of Public Health, the ATSDR, the EPA, the NIEHS and Tribal Leaders. Embedded in all of the MIT-SRP activities are training opportunities for undergraduates, graduate students and postdocs, thus supporting the next generation of environmental health scientists. The impact of the MIT-SRP is predicted to be significant, thanks to multidisciplinary collaboration among engineers, biomedical researchers, community outreach professionals, and experts in training and translation. Further, the technologies and approaches that will be developed can be broadly disseminated among Superfund sites and elsewhere. Taken together, the MIT-SRP will enable reduced risk, guidance for remediation, and support for policy decisions, thus having a direct and measurable impact on public health.